Biology subjects

Rapp, M. A.

Publications and source records attributed to Rapp, M. A..

4 recordsLinked to original sources

bioRxiv2025

Network Neuroscience of Human Multitasking: Local Features Matter

The neural basis of multitasking costs is subject to continuing debate. Cognitive theories assume that overlap of task representations may lead to between-task crosstalk in concurrent task processing and thus requires cognitive control. Recent research suggests that modality-based crosstalk contributes to multitasking costs, involving central overlap of modality-specific representations. Consistently increased costs for specific modality pairings (visual-vocal and auditory-manual vs. visual-manual and auditory-vocal) were demonstrated (modality-compatibility effect), which were recently linked to representational overlap in the auditory cortex. However, it remains unclear whether modality-based crosstalk emerges from overlapping patterns of global brain connectivity and whether resolving it requires additional involvement of cognitive control as reflected in the fronto-parietal control network. This preregistered functional imaging study investigates these questions in 64 healthy, young human adults. Specifically, we focus on the modality-compatibility effect in multitasking by employing functional connectivity (FC) analysis. First, we tested the FC similarity between the single-task networks. Second, we compared the strength of the control network in whole-brain FC between dual tasks. We found no evidence for different FC similarities of single-task networks between modality pairings and no additional involvement of the control network during dual tasks. However, post-hoc connectivity analysis revealed a brain-behavior correlation for the modality-compatibility effect in dual tasks. This effect was locally restricted to FC between lateral frontal and sensory auditory regions, providing evidence for the modality-based crosstalk theory. More generally, the findings suggest that robust behavioral differences in multitasking are not necessarily related to global functional connectivity differences but to local connectivity changes. SignificanceOur lives are dominated by multitasking. Understanding the neurocognitive mechanisms of multitasking and its associated limitations is relevant for safety-relevant consequences. Here, we investigate functional brain-connectivity patterns associated with modality-based crosstalk in multitasking, describing unintentional exchange of information between two tasks, leading to robust dual-task costs. Our network analyses revealed no significant difference between single or dual tasks with varying degrees of modality overlap on the whole-brain level. However, specific connections between cognitive control-related frontal and sensory-related regions were associated with individual multitasking performance, emphasizing that behavioral differences can arise from specific neural interactions rather than from widespread network reconfigurations. These findings advance our understanding of the underlying mechanisms responsible for modality-based crosstalk, providing practical implications for human-machine interactions.

neuroscience↗

bioRxiv2024

Multitasking practice eliminates modality-based interference by separating task representations in sensory brain regions

The debate on the neural basis of multitasking costs evolves around neural overlap between concurrently performed tasks. Recent evidence suggests that training-related reductions in representational overlap in fronto-parietal brain regions predict multitasking improvements. Cognitive theories assume that overlap of task representations may lead to unintended information exchange between tasks (i.e., crosstalk). Modality-based crosstalk was suggested as a source for multitasking costs in multisensory settings. Robust findings of increased costs for certain modality mappings may be explained by crosstalk between the stimulus modality in one task and sensory action consequences in the concurrently performed task. Whether modality-based crosstalk emerges from representational overlap in general fronto-parietal multitasking regions or modality-specific regions is not known yet. In this functional neuroimaging study, we investigate neural overlap in multitasking performance, focusing on modality compatibility by employing multivariate pattern analysis and modality-specific practice interventions in three groups (total N = 54). We observed significant differences between modality compatible and modality incompatible single-task representations, specifically in the auditory cortex but not in fronto-parietal regions. Notably, improved auditory decoding accuracy related to modality incompatible tasks was predictive of performance gains in the corresponding dual task along with complete elimination of modality-specific dual-task costs. This predictive relationship was evident only in the group practicing modality incompatible mappings, suggesting that specific practice on task sets with modality overlap influenced both neural representations and subsequent multitasking performance. This study contributes to the integration of cognitive theory and neuroscience and the role of task representations in dual-task interference. SignificanceIn a society dominated by multitasking, understanding its neurocognitive basis and plasticity is crucial for key aspects of work-related and everyday tasks. We investigate the neural mechanisms behind multitasking limitations, offering insights for targeted cognitive interventions. The study builds upon established theories of cognitive multitasking and imaging research, addressing the concept of modality-based crosstalk - the unintended exchange of modality-based information between tasks. Through functional brain imaging and pattern analysis, we examined how neural task representations contribute to performance costs in dual tasks with varying degrees of modality overlap. Notably, our findings demonstrate a practice-related decrease in neural overlap which is associated with substantial multitasking improvements, specifically in the auditory cortex, emphasizing the contribution of sensory regions to flexible multidimensional task representations.

neuroscience↗

bioRxiv2020

A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike

The SARS-CoV-2 spike employs mobile receptor-binding domains (RBDs) to engage the ACE2 receptor and to facilitate virus entry. Antibodies can engage RBD but some, such as CR3022, fail to inhibit entry despite nanomolar spike affinity. Here we show the SARS-CoV-2 spike to have low unfolding enthalpy at serological pH and up to 10-times more unfolding enthalpy at endosomal pH, where we observe significantly reduced CR3022 affinity. Cryo-EM structures -at serological and endosomal pH- delineated spike recognition of up to three ACE2 molecules, revealing RBD to freely adopt the up conformation. In the absence of ACE2, single-RBD-up conformations dominated at pH 5.5, resolving into a locked all-down conformation at lower pH. Notably, a pH-dependent refolding region (residues 824-858) at the spike-interdomain interface displayed dramatic structural rearrangements and mediated RBD positioning and spike shedding of antibodies like CR3022. An endosomal mechanism involving spike-conformational change can thus facilitate immune evasion from RBD- up-recognizing antibody. HighlightsO_LIReveal spike at serological pH to have only ~10% the unfolding enthalpy of a typical globular protein, explaining how antibodies like CR3022 can bind with avidity C_LIO_LIDefine an endosomal mechanism whereby spike binds ACE2, but sheds CR3022, enabling immune evasion from potentially neutralizing antibody C_LIO_LIDetermine cryo-EM structures of the SARS-CoV-2 spike along its endosomal entry pathway-at pH 5.5, 4.5, and 4.0, and in complexes with ACE2 receptor at pH 7.4 and 5.5 C_LIO_LIShow spike to exclusively adopt an all RBD-down conformation at the low pH of the late endosome-early lysosome C_LIO_LIReveal structural basis by which a switch domain mediates RBD position in response to pH C_LI

immunology↗

bioRxiv2020

Potent Neutralizing Monoclonal Antibodies Directed to Multiple Epitopes on the SARS-CoV-2 Spike

The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, "all RBD-down" conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

microbiology↗